The prior art discloses a modified release dosage product comprising a plurality of minicapsules (also termed “beads”) containing an active ingredient. The beads may be produced by mixing two different liquids which are not or are hardly soluble with each other and one of which is an aqueous liquid comprising gelatin or another gelling agent. The liquids are mixed and the resulting mixture is ejected through a nozzle which may have a single orifice. The nozzle may be vibrated as the mixture is ejected through it. The ejected mixture forms into drops which are more or less spherical and fall into a cooling gas (e.g. air) or into a cooling or hardening solution whereby the gelling agent gels and the drops become minicapsules. There are disclosed beads made by ejecting an oil-in-water emulsion whose aqueous phase comprises gelatin or another water-soluble polymer matrix material through a single orifice nozzle; the beads include an active agent and, after drying, can be described as a dried oil-in-water emulsion in which the dried aqueous phase comprises polymer matrix material. See for example WO 2004/084870, WO 2008/132712 and WO 2010/133609, all of which are incorporated herein in their entirety by reference. The size of the oil droplets of such prior art dried oil-in-water emulsions is not disclosed in the prior art but has been measured and found to be around 100 nm, or occasionally down to about 50 nm.
An X-ray tomography image of the bead of the above application WO 2010/133609 is shown in FIG. 9. The image illustrates the highly homogeneous nature of the bead i.e. the near universal dispersion of the oil phase throughout the aqueous phase.
Within the body dendritic cells play a vital role in the immune system. The main purpose of dendritic cells is to process antigen material and present the antigen to other cells of the immune system. Intestinal dendritic cells are found in the gut-associated lymphoid tissue, including the lamina propria of the small and large intestine, the isolated lymphoid follicles, the Peyer patches, and the mesenteric lymph nodes. Dendritic cells exist in two functionally distinct states: immature and mature cells. Immature dendritic cells are present in peripheral tissues and are mainly phagocytic cells; mature dendritic cells are found in lymphoid organs and are specialized in antigen presentation. Mature dendritic cells derive from immature cells after a maturation process that is initiated by inflammatory stimuli and that leads to a massive migration of dendritic cells to draining lymph nodes (Banchereau, Nature. 392:245-252; Steinman, Eur. J. Immunol. 37 S53-S60).
Several observations in humans and in mouse models of Inflammatory Bowel Disease suggest that dendritic cells may play a pathogenic role. Dysfunctional dendritic cells may: act by priming abnormal responses of T cells to the enteric flora in organized lymphoid tissues; sustain T cell reactivity within the inflamed mucosa through the interaction with T cells; and function as effector cells via the release of proinflammatory cytokines (Rescigno, J. Clin. Invest. 119:2441-2450).
Dendritic cells are potent immunostimulatory cells (Steinman1991) and intestinal dendritic cells actively participate in antigen capture across the intestinal epithelium by extending protrusions directly into the lumen for antigen sampling (Rescigno, Nat. Immunol. 2:361-367). These cells can take up and present both orally and intestinally administered antigens to naive T cells (Liu and MacPherson, 1991). Efficient capture and presentation of antigens by dendritic cells is thought to be central to the induction of an immune response (Colaco, 1999).
In the case of a known antigen as seen in celiac disease, a potential dendritic cell-based, antigen-specific strategy may take advantage of the ability of dendritic cells to expand and induce Tregs—the principal effectors of tolerance, which in turn suppress other dendritic cells that present disease-producing antigens (Steinman, Immunity. 29:319-324)